The proposed program will train M.D., Ph.D. and medical student investigators in state-of-the-art techniques to investigate the molecular and cellular mechanisms underlying central nervous system (CNS) injury. The trainees will be: 1) Physicians involved in the University of Pennsylvania Neurosurgical residency-training program, 2) Ph.D. scientists with prior training in molecular biology, or 3) selected medical students who are participating in Penn's unique Clinical Neuroscience Track program. This program will provide background and training in molecular neurobiology and an introduction to CNS disorders where these new techniques can be applied. This program will be a laboratory-based research-training program that includes experience in novel molecular biology techniques in an interactive and supportive setting. The institution has an extensive didactic program in basic and clinical neurosciences, neurodegeneration, CNS injury, and molecular biology including gene therapy, which will be individually designed for each trainee in order to supplement the laboratory experience. Each trainee will design and complete an independent project providing experience in design and analysis of experiments and in the presentation and publication of results. Weekly trainee research seminars and monthly faculty/trainee mini-symposia provide constant interchange and exchange between faculty trainers and trainees. This program will be run by individual faculty trainers who are the leaders in their field at the University of Pennsylvania, representing disciplines such as CNS ischemia and trauma, neurodegenerative diseases, inheritable neurological disorders, demyelinating diseases, epilepsy, neuroanesthesiology, molecular virology, gene therapy, and molecular pharmacology. Each trainee selects one laboratory for the primary research project but will have complete access to the other trainers for advise, technical assistance, and collaboration. Each trainer has independent NIH funding and all have active and internationally-recognized research programs. Core services available within the University of Pennsylvania, Wistar Institute, Children's Seashore House, and the Institute of Human Genome Therapy include protein sequencing, oligonucleotide synthesis, transgenic knock out/ knock in technology, automated DNA sequencing, viral vector construction, and gene therapy techniques. No funding mechanism currently exists at the University of Pennsylvania to support these trainees. The funding of this Brain Injury Training Grant (BITG) application will establish a novel and important infrastructure involving a highly collaborative faculty for the purpose of training future research scientists and clinicians in the state-of-the-art techniques related to an important clinical disease. [unreadable] [unreadable]